Allergy
ORIGINAL ARTICLE
AIRWAY DISEASES
RhinAsthma Patient Perspective: a short daily asthma and rhinitis QoL assessment F. Braido1,*, I. Baiardini1,*, E. Stagi2, N. Scichilone3, O. Rossi4, C. Lombardi5, E. Ridolo6, F. Gani7, S. Balestracci1, G. Girbino8, G. E. Senna9, A. Bordo1, M. K. Church10 & G. W. Canonica1 1
Allergy and Respiratory Diseases Clinic, University of Genoa, IRCCS-AOU San Martino, Genova; 2Epidemiology, Biostatistics and Clinical trials, National Cancer Research Institute, Genoa; 3Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, ‘Villa Sofia-Cervello’ Hospital, Palermo; 4Operative Immunoallergy Unit, A.O.U. Careggi, Florence; 5Pneumoallergology Unit, S. Orsola FBF Hospital, Brescia; 6Clinical Sciences, University of Parma, Parma; 7Allergy Unit, Respiratory Diseases Division, A.O.U. San Luigi, Torino; 8 Respiratory Department, University Hospital, Messina; 9Allergy Service, Verona Major Hospital, Verona, Italy; 10Department of Dermatology and Allergy, Allergy Centre Charite´, Charite´-Universita¨tsmedizin Berlin, Berlin, Germany
To cite this article: Braido F, Baiardini I, Stagi E, Scichilone N, Rossi O, Lombardi C, Ridolo E, Gani F, Balestracci S, Girbino G, Senna GE, Bordo A, Church MK, Canonica GW. RhinAsthma Patient Perspective: a short daily asthma and rhinitis QoL assessment. Allergy 2012; 67: 1443–1450.
Keywords assessment; asthma; daily practice; quality of life; rhinitis. Correspondence F. Braido, Allergy and Respiratory Diseases Clinic – DIMI – University of Genoa, IRCCSAOU San Martino, Pad. Maragliano, Largo Rosanna Benzi 10., 16132 Genova, Italy. Tel./Fax: +390105553524 E-mail:
[email protected] *These authors are contributed equally to this study. Accepted for publication 24 July 2012 DOI:10.1111/all.12014 Edited by: Hans-Uwe Simon
Abstract Background: The present study aimed to develop a short validated patient-completed questionnaire, the RhinAsthma Patient Perspective (RAPP), to assess the health-related quality of life (HRQoL) in patients with asthma and comorbid allergic rhinitis in clinical practice. Methods: A provisional RAPP questionnaire was formed from candidate items identified through retrospective analysis of 333 RHINASTHMA questionnaires. This was then tested on 150 asthma patients with allergic rhinitis. Results: Psychometric analyses identified eight items fitting a unidimensional model to form RAPP. Internal consistency (Cronbach’s alpha coefficient > 0.8) and agreement with RHINASTHMA (r = 0.31, P = 0.0001) were excellent. Criterion, discriminant, and convergent validity were good. Reliability in 47 stable patients was very good (intra-class and concordance correlation coefficients were 0.90 and 0.89, respectively). Responsiveness in 103 patients with health improvement or deterioration was significantly associated with changes in Global Rating Scale (r = 0.4965, P < 0.01), Rhinitis Visual Analogue Scale (r = 0.5722, P < 0.01) and asthma control test (r = 0.6483, P < 0.01). Minimal clinical difference in the analyzed population was 2. Conclusion: RhinAsthma Patient Perspective is a simple eight-question questionnaire with good measurement properties and sensitivity to health changes, which will provide a valid, reliable and standardized HRQoL measurement in patients with asthma and comorbid allergic rhinitis in clinical practice.
Health-related quality of life (HRQoL), defined as the impact of a disease and its treatment perceived by patients themselves, is considered to be an essential outcome measure in patients suffering from respiratory allergy. The use of questionnaires to evaluate HRQoL is recommended in guidelines for the diagnosis and management of both allergic rhinitis and asthma and by regulatory authorities in Europe and the United States. Furthermore, patients’ preferences and values are cornerstones in the Grade of Recommendations, Assessment Development and Evaluation (GRADE) system of formulating recommendations for diagnostic and therapeutic interventions (1).
Allergy 67 (2012) 1443–1450 © 2012 John Wiley & Sons A/S
Several disease-specific questionnaires have been developed and validated for use in allergic rhinitis and asthma research (1), and an increasing number of clinical trials evaluate the HRQoL, providing evidence of both the burden of disease and the effectiveness of treatments (1). However, more than half of patients with allergic rhinitis also have allergic asthma (2), and almost 90% of patients with allergic asthma also have allergic rhinitis (3). Consequently, the RHINASTHMA questionnaire (4) was developed as an instrument to assess HRQoL in patients with both conditions. This questionnaire contains 30 items and provides three factorial scores: Upper Airways (UA), Lower Airways (LA) and Respiratory Allergy
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Impact (RAI). In addition, it gives a composite score, the Global Summary (GS), which indicates the overall impact of the disease. Patients are asked to grade to what extent they have been bothered by each problem during the last 2 weeks using a 5-point Likert-type scale (not at all, a little, fairly, much, and very much). Answers are then converted into a score from 0 to 100, with a high score corresponding to poor HRQoL. Barriers to the use of current questionnaires in daily practice include their size and the complexity (5). In addition, their scoring systems are often based on an algorithm or a complex formula, making the results difficult to calculate by a physician in clinical practice or patient in a self-assessment context. Furthermore, the psychometric properties of the available questionnaires have been evaluated in patients’ populations, but not in the single patient (1). For a questionnaire to be clinically useful, not only it must be valid, reliable, and responsive in the single patient, but also it must be simple, quick to complete, easy to score and interpret, and it has to provide useful information for disease management (1, 5, 6). To date, there is only one Spanish questionnaire containing 10 questions, the Control of Allergic Rhinitis and Asthma Test (CARAT) (7), which has been developed to monitor the degree of control of allergic rhinitis and asthma. The aim of the current study was to develop a validated tool [RhinAsthma Patient Perspective (RAPP)] to assess HRQoL for asthma and allergic rhinitis in daily clinical practice. The RHINASTHMA questionnaire was used as a starting point for creating this tool for several reasons. First, its development procedure has involved a one-to-one unstructured interview of more than 200 adult outpatients suffering from respiratory allergy. Second, its item selection was made by 150 patients with a wide range of disease severity (8). Third, it has good psychometric properties and demonstrated reliability and responsiveness (4). And fourth, RHINASTHMA has been validated in Italian (4), English (9), and German (10), used widely in clinical trials and real life studies (11–13), and is endorsed in the GA2LEN recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma (1).
Materials and methods Phase 1: development of RAPP from RHINASTHMA RhinAsthma patient perspective development started from RHINASTHMA data sets of patients recruited in real life studies (8, 11). In order to identify the potentially delectable items, respecting the RHINASTHMA structure, a composite, iterative approach was adopted that took into account (i) percentage of unanswered questions; (ii) association between answers and questions and patient’s characteristics (sex, age, education, disease severity); (iii) floor and ceiling effects; (iv) item ranking; (v) item–total correlation; (vi) item–item correlation. Cognitive debriefing interviews with 10 patients suffering from rhinitis and asthma were performed in order to verify that the items resulted from the reduction phase (provisional RAPP) and the format was clear and easy to understand.
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Phase 2: RAPP validation Study design A cohort of 150 patients with prediagnosed concomitant asthma and allergic rhinitis were recruited for the study from nine allergology and pulmonology centers. The following inclusion criteria were adopted: adult (over 18 years of age); physician’s diagnosis of allergic asthma with concomitant allergic rhinitis according to GINA and ARIA classification (14, 15); comprehension of spoken and written Italian language; and availability and willingness to participate in the study. Patients suffering from any other respiratory or ear–nose–throat disorders were excluded. The study was approved by the Ethics Committee of the Azienda Ospedaliera Universitaria San Martino, Genoa (Protocol number 602/ 2010 May 31, 2010, Register number 48/10) and was conducted according to the Declaration of Helsinki. All participants gave signed informed consent at the beginning of the study. All patients were assessed twice with a 4-week interval between visits. At both visits, a physician collected a complete and accurate medical history and reported the ongoing therapy. Conventional spirometry according to ERS-ATS recommendations was performed (16). In addition, the patients completed the provisional RAPP questionnaire, RHINASTHMA (4), SF-12 (17), asthma control test (ACT) (18), and a Symptomatologic Visual Analog Scale (VAS) for rhinitis (19). At Visit 2, a Global Rating Scale (20) was completed to assess any change in health status. Validation process The following psychometric characteristics of the RAPP were evaluated: 1 Internal consistency: a measure of the homogeneity of a scale, was established calculating Cronbach’s correlation coefficient on the whole test. Good correlation was assumed if the coefficients were 0.70 or higher (21). Higher scores are recommended for use in the single patient (22, 23). 2 Criterion validity: the extent to which scores of the instrument are related to a criterion measure (22) was evaluated by two different analyses. First, a Spearman’s correlation coefficient was calculated in order to assess whether the RAPP measured the same construct as RHINASTHMA. Coefficients exceeding r = 0.7 were considered satisfactory (24). Second, the agreement between RAPP and RHINASTHMA was assessed by Bland and Altman plot (25). This technique evaluates whether two questionnaires behave in the same way across the entire scaling range of the instruments by plotting the difference between measurements made by the two instruments in the same individual against the mean of the two measurements. Discriminant validity: the instrument’s ability to differentiate between populations that are known or expected to differ was evaluated comparing patients according to ACT score and GINA (14) and ARIA (15) classification of severity. Convergent validity: the degree to which an instrument correlates with instruments measuring related
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constructs was performed by Spearman’s correlations to examine the relationships between RAPP and an established health status measure (SF-12) (26). Convergent validity is confirmed with correlations ranging from 0.4 to 0.8. Two instruments are considered too similar if the correlation is 0.8 or more (the tested instrument has no added value) (27). Scale’s dimensions: were tested by exploratory and confirmatory factor analysis. Exploratory factor analysis is a technique that permits to test the relationship between items and factors without imposing any a priori restriction on the loading values. The confirmatory analysis was used to verify the goodness of fit of the factor structure that emerged from exploratory analysis. To these purposes, the sample was divided into two same size subsamples G1 N = 75 and G2 N = 75. Exploratory factor analysis: the variables violated the assumption of multivariate normality (Mardia’s coefficient = 9.3), so the factors were extracted by a distributional free method, principal factor analysis. The following criteria were used to evaluate the factor solutions: explained variance and number of residuals greater than |0.10|. Confirmatory factor analysis: as the variables show a marked violation of normal multivariate distribution (Mardia’s coefficient = 6.02), minimum reported level (MRL) was used for estimation. Root-mean-square error of approximation (RMSEA), comparative fit index (CFI), and standardized root-mean-squared residual (SRMR) were used to assess fit. RMSEA values equal or 0.90 were considered satisfactory for the CFI (29). Finally, SRMR values 20 as criterion measure, to determine the RAPP score that indicates optimal HRQoL.
Results Phase 1: Development of RAPP from RHINASTHMA Questionnaires previously completed by 333 patients (125 males and 208 females, mean age 44.7 years, age range 16– 80 years) were used for the reduction phase. The rate of missing data was 0.70) both at Visit 1 (r = 0.78, P < 0.01) and at Visit 2 (r = 0.86, P < 0.01). The Bland and Altman plot (Fig. 1) showed a very stable and consistent relationship across the scaling range (r = 0.3133, P = 0.0001). Discriminant validity: the eight-item version of RAPP was able to discriminate between patients on the basis of asthma severity, asthma control level, and rhinitis severity (Table 2). Convergent validity: RAPP scores showed a significant, moderate correlations with the Physical Component Score of SF-12 both at Visit 1 (r = 0.62, P < 0.01) and at Visit 2 (r = 0.62, P < 0.01). Significant, weak correlations were found between RAPP and the Mental Component Score of SF-12 both at Visit 1 (r = 0.48, P < 0.01) and at Visit 2 (r = 0.34, P < 0.01). All the associations were in the expected direction. Scale’s dimensions: to probe the underlining RAPP structure, exploratory factor analysis was conducted on the first subsample of the 75 subjects. The chosen solution revealed one factor that absorbed 57.4% of the total variance; furthermore, only one residual was greater than |
Cronbach’s alpha coefficient
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Table 1 Cronbach’s alpha coefficients of the provisional RhinAsthma patient perspective (RAPP) (10-item version)
–100
Table S1 shows the results of the development procedure indicating the characteristics that determined item selection. The item-to-total correlation ranged from 0.44 to 0.72 for GS, from 0.69 to 0.81 for UA, from 0.56 to 0.84 for LA, and from 0.53 to 0.72 for RAI. The item-to-item correlations ranged from 0.12 to 0.80. Correlations 0.70 were seen between six pairs of items (indicating that one of each pair may be redundant). Owing to the high correlation, items describing nasal symptoms (4) were combined in a unique item. The same procedure was adopted for ocular symptoms (4), respiratory problems (4), sleep disturbance (2), and daily activity limitations (3) giving 5 rather than 17 items. The above-described iterative process allowed the selection of 10 items for inclusion in the provisional RAPP. The cognitive debriefing interviews of the provisional RAPP were conducted on 10 patients and showed that both the items and the format in which they were presented were clear and easy to understand.
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40 Mean score
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Figure 1 Bland and Altman plot of RhinAsthma patient perspective and RHINASTHMA scores. The correlation for a linear regression was r = 0.3133, P = 0.0001 (n = 150)
0.10| (Table S2). The confirmatory factor analysis conducted with Mplus 6.0 (Muthe´n, LK and Muthe´n, B. MPLUS User’s guide. Los Angeles, CA, USA, 2004) on the second subsample of 75 participants (Fig. S1) confirmed the one-dimensional RAPP structure. The introduction of correlations between errors of items 1 and 2 has improved the model’s goodness-of-fit indexes, which were generally good: RMSEA = 0.08; SRMR = 0.07; CFI = 0.95. Reliability: was assessed in 47 patients reporting an unchanged health status at Visit 2 (GRS = 0). An excel-
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lent reproducibility was found, as testified by ICC = 0.90 and CCC = 0.89. Responsiveness: was assessed in 103 patients with a health improvement or deterioration, measured by GRS (GRS 6¼ 0 > 1 and GRS < 1). Changes in RAPP scores were significantly associated with changes in GRS (r = 0.50, P < 0.01), VAS (r = 0.57, P < 0.01), and ACT (r = 0.65, P < 0.01). All the associations were in the expected direction. Clinical significance: results of the ROC analyses are presented in Table 3. A 2-point difference or change in RAPP maximizes sensitivity, specificity, and the number of individuals correctly classified. No significant difference was reported in RAPP scores between smokers, former smokers, and nonsmokers (ANOVA Fischer’s test. Visit 1: P = 0.663; Visit 2: P = 0.596) or on the basis of degree of education (ANOVA Fischer’s test. Visit 1: P = 0.916; Visit 2: P = 0.323). No significant associations were found between age and RAPP scores (Spearman’s correlation. Visit 1: r = 0.014; Visit 2, r = 0.10). The frequency distribution of answers (Visit 1 and Visit 2) shows that the entire scaling range was used (Fig. 2) and that all possible RAPP scores were obtained (Fig. 3).
Table 3 The minimal important difference RhinAsthma patient perspective (RAPP) obtained by receiver operating characteristics analysis of different cutoffs of the global rating of change
Cutoff point
Sensitivity (%)
Specificity (%)
Correctly classified (%)
0 1 2* 3 4 5 6 7 8 9 10
84.11 71.96 62.62 52.34 47.66 42.99 34.58 31.78 28.04 19.63 17.76
23.81 50.00 64.29 80.95 85.71 85.71 92.86 97.62 97.62 97.62 97.62
67.11 65.77 63.09 60.40 58.39 55.03 51.01 50.34 47.65 41.61 40.27
The entire cohort for one dichotomization point (i.e., ‘no change’ vs ‘any improvement or deterioration’ measured by the GRS) was used. *Cutoff point chosen.
RAPP scoring
Table 2 RhinAsthma patient perspective (RAPP) discriminant validity RAPP scores
Asthma Intermittent Persistent Moderate persistent Severe persistent P-value* ACT Totally controlled Well controlled Uncontrolled P-value* Rhinitis Intermittent Persistent P-value† Rhinitis severity Moderate Severe P-value†
Visit 1
Visit 2
33.79 27.96 45.31 49.15 0.0008
23.57 17.76 29.55 50.85
